title: The selective serotonin re-uptake inhibitor escitalopram modulates the panic response to cholecystokinin tetrapeptide in healthy men depending on 5-HTTLPR genotype.
abstract: Selective serotonin re-uptake inhibitors, such as escitalopram, are currently the treatment of choice for patients with panic disorder. The panic response to intravenous cholecystokinin tetrapeptide, a potentially useful paradigm for volunteer translational studies, has so far not been investigated in healthy man after respective pre-treatment. In a double-blind, placebo-controlled, randomized, within subject cross-over design 30 healthy young men, 15 each with the long/long or short/short genotype for the serotonin transporter linked polymorphic region, were pre-treated with 10mg/d of escitalopram orally for six weeks and then challenged with 50 microg of cholecystokinin tetrapeptide. The primary outcome measure was the increase of Acute Panic Inventory ratings by cholecystokinin tetrapeptide. The increase of anxiety, tension and stress hormone secretion were secondary outcome measures. A significant treatment by genotype effect on the increases of Acute Panic Inventory ratings emerged. Panic induced by cholecystokinin tetrapeptide was significantly more pronounced in the short/short genotype subjects under escitalopram vs. placebo pre-treatment. With the exception of significantly elevated serum prolactin after escitalopram, no effects in the secondary outcome measures were detected. Contrary to our expectation, no inhibitory effect of escitalopram upon panic symptoms elicited by choleystokinin tetrapeptide could be demonstrated in healthy men. These findings do not support the potential usefulness of this panic model for proof-of-concept studies. The biological underpinnings of the increased panic symptoms after escitalopram in our volunteers with short/short genotype need further research.
authors.affiliation: University Hospital Hamburg-Eppendorf, Department of Psychiatry, Martinistrasse 52, D-20246 Hamburg, Germany. kellner@uke.uni-hamburg.de
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
authors.forename: Christoph
authors.initials: C
authors.lastname: Muhtz
authors.forename: Cüneyt
authors.initials: C
authors.lastname: Demiralay
authors.forename: Jana
authors.initials: J
authors.lastname: Husemann
authors.forename: Wiebke
authors.initials: W
authors.lastname: Koelsch
authors.forename: Alexander
authors.initials: A
authors.lastname: Yassouridis
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001007:Anxiety / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D015283:Citalopram / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D010200:Panic / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D012016:Reference Values; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013315:Stress, Psychological / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D013758:Tetragastrin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D015283:Citalopram; D011388:Prolactin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D013758:Tetragastrin; C493230:SLC6A4 protein, human